{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,16]],"date-time":"2026-04-16T02:34:12Z","timestamp":1776306852561,"version":"3.50.1"},"reference-count":92,"publisher":"The Company of Biologists","issue":"15","license":[{"start":{"date-parts":[[2019,2,1]],"date-time":"2019-02-01T00:00:00Z","timestamp":1548979200000},"content-version":"vor","delay-in-days":184,"URL":"http:\/\/www.biologists.com\/user-licence-1-1\/"}],"funder":[{"DOI":"10.13039\/501100003977","name":"Israel Science Foundation","doi-asserted-by":"publisher","award":["228\/14"],"award-info":[{"award-number":["228\/14"]}],"id":[{"id":"10.13039\/501100003977","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003977","name":"Israel Science Foundation","doi-asserted-by":"publisher","award":["1019\/15"],"award-info":[{"award-number":["1019\/15"]}],"id":[{"id":"10.13039\/501100003977","id-type":"DOI","asserted-by":"publisher"}]},{"name":"INCPM (Israel National Center for Personalized Medicine) Israel Science Foundation","award":["2246\/16"],"award-info":[{"award-number":["2246\/16"]}]},{"name":"Israel Science Foundation-National Natural Science Foundation of China","award":["2469\/16"],"award-info":[{"award-number":["2469\/16"]}]},{"DOI":"10.13039\/501100001742","name":"United States-Israel Binational Science Foundation","doi-asserted-by":"publisher","award":["2013016"],"award-info":[{"award-number":["2013016"]}],"id":[{"id":"10.13039\/501100001742","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2018,8,1]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n               <jats:p>The synchronized differentiation of neuronal and vascular tissues is crucial for normal organ development and function, although there is limited information about the mechanisms regulating the coordinated development of these tissues. The choroid vasculature of the eye serves as the main blood supply to the metabolically active photoreceptors, and develops together with the retinal pigmented epithelium (RPE). Here, we describe a novel regulatory relationship between the RPE transcription factors Pax6 and Sox9 that controls the timing of RPE differentiation and the adjacent choroid maturation. We used a novel machine learning algorithm tool to analyze high resolution imaging of the choroid in Pax6 and Sox9 conditional mutant mice. Additional unbiased transcriptomic analyses in mutant mice and RPE cells generated from human embryonic stem cells, as well as chromatin immunoprecipitation and high-throughput analyses, revealed secreted factors that are regulated by Pax6 and Sox9. These factors might be involved in choroid development and in the pathogenesis of the common blinding disease: age-related macular degeneration (AMD).<\/jats:p>","DOI":"10.1242\/dev.163691","type":"journal-article","created":{"date-parts":[[2018,7,9]],"date-time":"2018-07-09T11:35:12Z","timestamp":1531136112000},"source":"Crossref","is-referenced-by-count":26,"title":["Pax6 regulation of <i>Sox9<\/i> in the mouse retinal pigmented epithelium controls its timely differentiation and choroid vasculature development"],"prefix":"10.1242","volume":"145","author":[{"given":"Yamit","family":"Cohen-Tayar","sequence":"first","affiliation":[{"name":"Sagol School of Neurosciences, Tel Aviv University 1 Department of Human Molecular Genetics and Biochemistry, Sackler Faculty of Medicine , , Tel Aviv 69978 , Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hadar","family":"Cohen","sequence":"additional","affiliation":[{"name":"Raymond and Beverly Sackler School of Physics and Astronomy, Tel-Aviv University 2 Department of Particle Physics , , Tel Aviv 69978 , Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yulia","family":"Mitiagin","sequence":"additional","affiliation":[{"name":"Biochemistry and Biophysics school, George S. Wise Faculty of Life Sciences, Tel-Aviv University 3 Department of Neurobiology , , Tel Aviv 69978 , Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zohar","family":"Abravanel","sequence":"additional","affiliation":[{"name":"Sagol School of Neurosciences, Tel Aviv University 1 Department of Human Molecular Genetics and Biochemistry, Sackler Faculty of Medicine , , Tel Aviv 69978 , Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Carmit","family":"Levy","sequence":"additional","affiliation":[{"name":"Sagol School of Neurosciences, Tel Aviv University 1 Department of Human Molecular Genetics and Biochemistry, Sackler Faculty of Medicine , , Tel Aviv 69978 , Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Masha","family":"Idelson","sequence":"additional","affiliation":[{"name":"Hadassah-Hebrew University Medical Center 4 The Hadassah Human Embryonic Stem Cell Research Center, The Goldyne Savad Institute of Gene Therapy and The Department of Obstetrics and Gynecology , , 9112001 Jerusalem , Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Benjamin","family":"Reubinoff","sequence":"additional","affiliation":[{"name":"Hadassah-Hebrew University Medical Center 4 The Hadassah Human Embryonic Stem Cell Research Center, The Goldyne Savad Institute of Gene Therapy and The Department of Obstetrics and Gynecology , , 9112001 Jerusalem , Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shalev","family":"Itzkovitz","sequence":"additional","affiliation":[{"name":"Weizmann Institute of Science 76100 5 Department of Molecular Cell Biology , , Rehovot , Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shaul","family":"Raviv","sequence":"additional","affiliation":[{"name":"Sagol School of Neurosciences, Tel Aviv University 1 Department of Human Molecular Genetics and Biochemistry, Sackler Faculty of Medicine , , Tel Aviv 69978 , Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Klaus H.","family":"Kaestner","sequence":"additional","affiliation":[{"name":"Department of Genetics, University of Pennsylvania Perelman School of Medicine, 12-126 Smilow Center for Translational Research 6 , 3400 Civic Center Blvd, Philadelphia, PA 19104-6145 , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4042-214X","authenticated-orcid":false,"given":"Pablo","family":"Blinder","sequence":"additional","affiliation":[{"name":"Biochemistry and Biophysics school, George S. Wise Faculty of Life Sciences, Tel-Aviv University 3 Department of Neurobiology , , Tel Aviv 69978 , Israel"},{"name":"Sagol School for Neuroscience, Tel-Aviv University 7 , Tel Aviv 69978 , Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3440-1286","authenticated-orcid":false,"given":"Ran","family":"Elkon","sequence":"additional","affiliation":[{"name":"Sagol School of Neurosciences, Tel Aviv University 1 Department of Human Molecular Genetics and Biochemistry, Sackler Faculty of Medicine , , Tel Aviv 69978 , Israel"},{"name":"Sagol School for Neuroscience, Tel-Aviv University 7 , Tel Aviv 69978 , Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5364-6898","authenticated-orcid":false,"given":"Ruth","family":"Ashery-Padan","sequence":"additional","affiliation":[{"name":"Sagol School of Neurosciences, Tel Aviv University 1 Department of Human Molecular Genetics and Biochemistry, Sackler Faculty of Medicine , , Tel Aviv 69978 , Israel"},{"name":"Sagol School for Neuroscience, Tel-Aviv University 7 , Tel Aviv 69978 , Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"237","published-online":{"date-parts":[[2018,8,9]]},"reference":[{"key":"2024061113415831400_DEV163691C1","doi-asserted-by":"publisher","first-page":"e0144597","DOI":"10.1371\/journal.pone.0144597","article-title":"Pax6 inactivation in the adult pancreas reveals ghrelin as endocrine cell maturation marker","volume":"10","author":"Ahmad","year":"2015","journal-title":"PLoS ONE"},{"key":"2024061113415831400_DEV163691C2","doi-asserted-by":"publisher","first-page":"2813","DOI":"10.1101\/gad.1017802","article-title":"The transcription factor Sox9 has essential roles in successive steps of the chondrocyte differentiation pathway and is required for expression of Sox5 and Sox6","volume":"16","author":"Akiyama","year":"2002","journal-title":"Genes Dev."},{"key":"2024061113415831400_DEV163691C3","doi-asserted-by":"publisher","first-page":"993","DOI":"10.1038\/nature05249","article-title":"Corneal avascularity is due to soluble VEGF receptor-1","volume":"443","author":"Ambati","year":"2006","journal-title":"Nature"},{"key":"2024061113415831400_DEV163691C4","doi-asserted-by":"publisher","first-page":"225","DOI":"10.1387\/ijdb.160393ra","article-title":"The retinal pigmented epithelium \u2013 from basic developmental biology research to translational approaches","volume":"61","author":"Amram","year":"2017","journal-title":"Int. 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